Blood pressure-lowering effects of a Bowman-Birk inhibitor and its derived peptides in normotensive and hypertensive rats

Abstract

Bioactive plant peptides have received considerable interest as potential antihypertensive agents with potentially fewer side effects than antihypertensive drugs. Here, the blood pressure-lowering effects of the Bowman-Birk protease inhibitor, BTCI, and its derived peptides, PepChy and PepTry, were investigated using normotensive (Wistar-WR) and spontaneously hypertensive rats (SHR). BTCI inhibited the proteases trypsin and chymotrypsin, respectively, at 6 µM and 40 µM, a 10-fold greater inhibition than observed with PepTry (60 µM) and PepChy (400 µM). These molecules also inhibited angiotensin converting enzyme (ACE) with IC 50 values of 54.6 ± 2.9; 24.7 ± 1.1; and 24.4 ± 1.1 µM, respectively, occluding its catalytic site, as indicated by molecular docking simulation, mainly for PepChy and PepTry. Gavage administration of BTCI and the peptides promoted a decrease of systolic and diastolic blood pressure and an increase of renal and aortic vascular conductance. These effects were more expressive in SHR than in WR. Additionally, BTCI, PepChy and PepTry promoted coronary vasodilation and negative inotropic effects in isolated perfused hearts. The nitric oxide synthase inhibitor blunted the BTCI and PepChy, with no cardiac effects on PepTry. The findings of this study indicate a therapeutic potential of BTCI and its related peptides in the treatment of hypertension.

In Vivo Diuretic Activity and Anti-Hypertensive Potential of Hibiscus sabdariffa Extract by Inhibition of Angiotensin-Converting Enzyme and Hypertension Precursor Enzymes

“…This study confirms the hypotensive and anti-hypertensive effects of the Bowman-Birk protease inhibitor, particularly inhibiting trypsin and chymotrypsin [32]. This property contributes to the bioavailability of peptides with ACE inhibitory activity [33]. By inhibiting XO, HS extract may be useful in managing hyperuricemia, an index of gout, and preventing downstream events, including increased reactive oxygen species production, activation of the renin/angiotensin pathway, and inactivation of bradykinin, which links hyperuricemia to hypertension [34].…”

Bowman-Birk Inhibitors: Insights into Family of Multifunctional Proteins and Peptides with Potential Therapeutical Applications

“…The authors hypothesized that BTCI might function as a carrier for bradykinin in the blood in order to protect it from proteases. Antihypertensive and vasodilator effects of BTCI and its two related disulfide-bridged nonapeptides, reflecting its trypsin and chymotrypsin binding loops, are also demonstrated in the further study [231]. BTCI and both synthetic peptides promote a decrease of systolic (SBP) and diastolic blood pressure (DBP) and renal and aortic vasodilation in normotensive (Wistar-WR) and spontaneously hypertensive rats (SHR) after gavage administration.…”

Plant Protease Inhibitors as Emerging Antimicrobial Peptide Agents: A Comprehensive Review

“…Notably, several low-molecular PPIs from plants contain a high content of cysteine residues that form disulfide bridges that confer resistance to heat treatment, extreme pH or ionic forces, and proteolysis [62,[73][74][75][76][77]. Owing to their multifunctionality and remarkable physicochemical properties, PPIs have found a wide array of applications in biotechnology and biomedicine, including their use as antimicrobial agents [21,[78][79][80] (Figure 4). Despite their high stability, the presence of multiple cysteine residues involved in disulfide bridges often complicates the production of these molecules, requiring a comprehensive understanding of their folding mechanisms and three-dimensional structure [81,82].…”